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Biomedical subjects

M I Lewis

Publications and source records attributed to M I Lewis.

At least 19 recordsLinked to original sources

Influences of IGF-I gene disruption on the cellular profile of the diaphragm.

The impact of a targeted disruption of the Igf1 gene, encoding the insulin-like growth factor I (IGF-I), on diaphragm (DIA) cellularity was studied in 2-mo-old homozygous mutant [IGF-I(-/-)] mice and their wild-type [WT; i.e., IGF-I(+/+)] littermates. DIA fiber types were classified histochemically. DIA fiber cross-sectional areas (CSA) were determined from digitized muscle sections, and fiber succinate dehydrogenase (SDH) activity was determined histochemically using a microdensitometric procedure. An acidic ATPase reaction was used to visualize capillaries. Myosin heavy chain (MyHC) isoforms were identified by SDS-PAGE, and their proportions were determined by scanning densitometry. The body weight of IGF-I(-/-) animals was 32% that of WT littermates. DIA fiber type proportions were unchanged between the groups. The CSAs of types I, IIa, and IIx DIA fibers of IGF-I(-/-) mutants were 63, 68, and 65%, respectively, those of WT animals (P < 0.001). The DIA thickness and the number of fibers spanning its entire thickness were reduced by 36 and 25%, respectively, in IGF-I(-/-) mice (P < 0. 001). SDH activity was significantly increased in all three types of DIA fibers of IGF-I(-/-) mutants (P < 0.05). The number of capillaries per fiber was reduced approximately 30% in IGF-I(-/-) animals, whereas the capillary density was preserved. The proportions of MyHC isoforms were similar between the groups. Muscle hypoplasia likely reflects the importance of IGF-I on cell proliferation, differentiation, and apoptosis (alone or in combination) during development, although reduced cell size highlights the importance of IGF-I on rate and/or maintenance of DIA fiber growth in the postnatal state. Reduced capillarity may result from both direct and indirect influences on angiogenesis. Improved oxidative capacity likely reflects DIA compensatory mechanisms in IGF-I(-/-) mutants.

Animals↗

Functional, cellular, and biochemical adaptations to elastase-induced emphysema in hamster medial scalene.

The scalene has been reported to be an accessory inspiratory muscle in the hamster. We hypothesize that with the chronic loads and/or dynamic hyperinflation associated with emphysema (Emp), the scalene will be actively recruited, resulting in functional, cellular, and biochemical adaptations. Emp was induced in adult hamsters. Inspiratory electromyogram (EMG) activity was recorded from the medial scalene and costal diaphragm. Isometric contractile and fatigue properties were evaluated in vitro. Muscle fibers were classified histochemically and immunohistochemically. Individual fiber cross-sectional areas (CSA) and succinate dehydrogenase (SDH) activities were determined quantitatively. Myosin heavy chain (MHC) isoforms were identified by SDS-PAGE, and their proportions were determined by scanning densitometry. All Emp animals exhibited spontaneous scalene inspiratory EMG activity during quiet breathing, whereas the scalene muscles of controls (Ctl) were silent. There were no differences in contractile and fatigue properties of the scalene between Ctl and Emp. In Emp, the relative amount of MHC(2A) was 15% higher whereas that of MHC(2X) was 14% lower compared with Ctl. Similarly, the proportion of type IIa fibers increased significantly in Emp animals with a concomitant decrease in IIx fibers. CSA of type IIx fibers were significantly smaller in Emp compared with Ctl. SDH activities of all fiber types were significantly increased by 53 to 63% in Emp. We conclude that with Emp the actively recruited scalene exhibits primary-like inspiratory activity in the hamster. Adaptations of the scalene with Emp likely relate both to increased loads and to factors intrinsic to muscle architecture and chest mechanics.

Acclimatization↗

Pulmonary physiologic changes of morbid obesity.

OBJECTIVE: Our objective was to study the effects of extreme obesity on pulmonary function tests and the effects of smoking on these variables in a population group larger than has previously been reported. DESIGN: Retrospective data analysis. SETTING: Academic medical center. PATIENTS: Forty-three patients with extreme obesity [ratio of weight in kilograms to height in centimeters greater than 0.9 (W/H)] who underwent pulmonary function testing at Cedars-Sinai on an out-patient or in-patient basis during the period of 1979 to 1 997. MEASUREMENTS AND RESULTS: Patients underwent standard pulmonary function testing. The patients were divided into 2 groups based on the W/H ratio: group A (0.9-0.99) and group B (greater than 1.0). Chart review was performed to identify pertinent history/co-morbidities. The independent effects of smoking between each group's patients were assessed. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), expiratory reserve volume (ERV), functional residual capacity (FRC), maximum voluntary ventilation (MVV), and forced expiratory flow during midexpiratory phase (FEF25-75%,) were significantly reduced in both groups. Single-breath diffusing capacity for carbon monoxide (DLCO) and the volume of gas into which the single-breath of carbon monoxide and helium was diluted were not elevated. Smoking did not account for the results in group A but did seem to partially explain the decrease in FVC, FEV1, and FEF25-75% in group B. CONCLUSIONS: Extreme obesity is associated with a reduction in ERV, FVC, FEV1, FRC, FEF25-75%, and MVV. However, contrary to prior reports, D(LCO) is not elevated. These effects are only partially explained by smoking.

Adolescent↗

Alterations in diaphragm contractility after nandrolone administration: an analysis of potential mechanisms.

The aim of this study was to evaluate the potential mechanisms underlying the improved contractility of the diaphragm (Dia) in adult intact male hamsters after nandrolone (Nan) administration, given subcutaneously over 4 wk via a controlled-release capsule (initial dose: 4.5 mg. kg-1. day-1; with weight gain, final dose: 2.7 mg. kg-1. day-1). Control (Ctl) animals received blank capsules. Isometric contractile properties of the Dia were determined in vitro after 4 wk. The maximum velocity of unloaded shortening (Vo) was determined in vitro by means of the slack test. Dia fibers were classified histochemically on the basis of myofibrillar ATPase staining and fiber cross-sectional area (CSA), and the relative interstitial space was quantitated. Ca2+-activated myosin ATPase activity was determined by quantitative histochemistry in individual diaphragm fibers. Myosin heavy chain (MHC) isoforms were identified electrophoretically, and their proportions were determined by using scanning densitometry. Peak twitch and tetanic forces, as well as Vo, were significantly greater in Nan animals compared with Ctl. The proportion of type IIa Dia fibers was significantly increased in Nan animals. Nan increased the CSA of all fiber types (26-47%), whereas the relative interstitial space decreased. The relative contribution of fiber types to total costal Dia area was preserved between the groups. Proportions of MHC isoforms were similar between the groups. There was a tendency for increased expression of MHC2B with Nan. Ca2+-activated myosin ATPase activity was increased 35-39% in all fiber types in Nan animals. We conclude that, after Nan administration, the increase in Dia specific force results from the relatively greater Dia CSA occupied by hypertrophied muscle fibers, whereas the increased ATPase activity promotes a higher rate of cross-bridge turnover and thus increased Vo. We speculate that Nan in supraphysiological doses have the potential to offset or ameliorate conditions associated with enhanced proteolysis and disordered protein turnover.

Anabolic Agents↗

Respiratory work in elastase treated hamsters.

Biomechanical adaptations of the diaphragm in the hamster model of emphysema are similar to those observed in skeletal muscle with exercise training. The aim of this study was to evaluate whether the dynamic pressure-volume (PV) work of breathing in hamsters with elastase-induced emphysema may contribute to these adaptations. PV work in elastase treated animals was compared to healthy controls. The studies were performed in adult hamsters 14-16 months following intratracheal administration of elastase (elastase treated group, ET) or saline (control group, CTL). Airway and esophageal pressures and air flows were measured during spontaneous breathing in anesthetized, supine animals. Pulmonary work (WL) was computed from transpulmonary pressures and airflows. Functional residual capacity (FRC) and total lung capacity (TLC; defined as volume at 25 cmH2O) in ET were increased 2 and 1.8 times, respectively, compared with CTL. Averaged tidal volume (VT) and inspiratory flows were comparable between groups. Total work of breathing (WT) normalized per ml VT was not significantly affected with elastase treatment but the pulmonary elastance work (WE) was significantly less in ET animals than controls (0.88 +/- 0.61 g cm(-2) vs. 1.63 +/- 0.32). Pulmonary resistive work was not significantly different between ET and CTL animals. These results suggest that biomechanical adaptations of the diaphragm observed in ET hamsters are caused by mechanisms other than the changes in dynamic mechanical properties of the lung following elastase treatment.

Animals↗

Cellular adaptations of skeletal muscles to cyclosporine.

The aim of this study was to evaluate the cellular response of the diaphragm, extensor digitorum longus (EDL), and soleus (Sol) muscles to clinically relevant doses of cyclosporine administered to male rats over 4 wk. Control rats were provided with vehicle only. Muscle fiber types, cross-sectional areas, indexes of capillarity, and succinate dehydrogenase (SDH) activity were determined by quantitative histochemistry. Myosin heavy chain isoforms were identified by SDS-PAGE, and their proportions were measured by scanning densitometry. Serum cyclosporine level, 20-24 h after the last dose of cyclosporine, was 145 +/- 81 ng/ml. Final body weight and muscle mass were similar between the cyclosporine and control groups. In the diaphragm, EDL, and Sol, no differences were observed between the groups with regard to fiber type proportions, fiber cross-sectional areas, and proportions of myosin heavy chain isoforms. In the EDL, reductions, both in SDH activity in type I, IIx, and IIb fibers (-26 to -37%) and in indexes of capillarity (-18 to -37%), were noted. In the Sol, SDH activity and capillarity were similar between the groups. In the diaphragm of cyclosporine-treated rats, there was significant reduction in the number of capillaries around individual fibers (-5%), whereas levels of SDH activity tended to be lower. This suggests that activation history may in part determine muscle-specific responses to cyclosporine. We speculate that reduced oxidative activity and capillarity of some limb muscles contribute to reduced exercise capacity and the "deconditioned state" observed in patients receiving cyclosporine after successful solid-organ transplantation.

Animals↗

IGF-I and/or growth hormone preserve diaphragm fiber size with moderate malnutrition.

Resistance to the anabolic effects of growth hormone (GH) occurs with severe caloric deficit. This study examined whether moderate caloric deficit (50% of daily intake for 7 days) in the adolescent rat exceeds a critical threshold for GH action and whether a combination of GH and insulin-like growth factor I (IGF-I) would have enhanced anabolic effects on the diaphragm (Dia). Five groups of rats (4 wk old) were studied: 1) control (Ctl), 2) nutritionally deprived (ND), 3) ND + GH, 4) ND + IGF-I, and 5) ND + GH + IGF-I. IGF-I was given by continuous infusion (200 microg/day). GH was injected subcutaneously (250 microg every 12 h). Contractile and fatigue properties of the Dia were determined in vitro. Quantitative histochemical methods were used to determine Dia fiber type proportions, cross-sectional areas, and succinate dehydrogenase activities. The body weight of Ctl rats increased 46% compared with 7% in ND animals, whereas that of ND rats receiving growth factors was intermediate. Serum IGF-I levels were reduced 54% in ND animals and maintained with the provision of growth factors. Dia fatigue resistance was improved in ND animals receiving growth factors. There were no differences in Dia contractile properties, fiber type proportions, or succinate dehydrogenase activities across groups. ND resulted in atrophy/growth arrest of all Dia fibers (20-32%) compared with Ctl. Administration of IGF-I and/or GH completely prevented atrophy/growth arrest of all Dia fibers. No additive or synergistic effects were noted. We propose that these growth factors may provide useful short-term adjunctive nutritional support in circumstances in which the provision of optimal nutrition may be delayed or inadequate.

Animals↗

FK 506 'rescue' immunosuppression for obliterative bronchiolitis after lung transplantation.

PRELIMINARY EXPERIENCE: In a consecutive case series (level V evidence) involving 10 recipients of unilateral lung transplantation (LT) with bronchiolitis obliterans, in conjunction with Fujisawa protocol 93-0-003, the physiologic responses to FK 506 (tacrolimus) "rescue" immunosuppression were assessed. Recipients were 22+/-18 months post-LT and demonstrated progressive allograft dysfunction that was refractory to pulsed-dose methylprednisolone therapy. All recipients received induction immunosuppression with Minnesota antilymphocyte globulin (10 to 15 mg/kg/d) for 5 to 10 days, cyclosporine (CsA) (whole-blood Abbott TDX fluorescence polarization immunoassay (Abbott Inc, Abbott Park, IL)=600 to 800 ng/mL), azathioprine (2 mg/kg/d), and prednisone (tapered to 0.2 mg/kg/d). The "rescue" regimen consisted of oral FK 506 adjusted to maintain a whole-blood Abbott IMX microparticle enzyme immunoassay (Abbott Inc, Abbott Park, IL) of 10 to 15 ng/mL with an initial increase in prednisone (1.0 mg/kg/d) during conversion that was subsequently tapered to 0.2 mg/kg/d. Spirometry was performed monthly in accordance with accepted American Thoracic Society criteria. Recipients were classified in accordance with the International Society for Heart and Lung Transplantation (ISHLT) "Working Formulation for Standardization of Nomenclature and for Clinical Staging of Chronic Dysfunction in Lung Allografts" as stages Ib (n=2), IIb (n=4), and IIIb (n=4) upon entry to the protocol. The deltaFEV1/month relationships during CsA- and FK 506-based regimens were analyzed by linear regression and compared by signed rank test (p<0.05). RESULTS: The deltaFEV1/month slopes were -0.0687+/-0.0221 and +0.0300+/-0.033 L/mo (mean+/-SEM) for CsA and FK 506, respectively (p=0.037). Although no significant spirometric improvement was noted in most recipients, no further decline in FEV1 occurred after conversion to FK 506. Recipients with less severe chronic dysfunction (ie, obliterative bronchiolitis [OB] stages Ib and IIb) stabilized their spirometric indexes at higher levels. Two recipients with OB stage IIIb died of hypercapnic respiratory failure at 6 and 8 months after conversion. CONCLUSIONS: The deltaFEV1/mo slopes stabilized after FK 506 conversion. Earlier conversion may be beneficial in stabilizing FEV1 at a higher plateau. Significant economic impact may be anticipated with FK 506 compared to alternative cytolytic strategies for OB. However, multicenter prospective controlled investigations are necessary to further address the potential role of FK 506 after LT (level I evidence). Furthermore, the ISHLT "Staging of OB Syndrome" may have significant clinical implications vis-à-vis prognosis and potential therapies.

Bronchiolitis Obliterans↗

Effect of insulin-like growth factor I and/or growth hormone on diaphragm of malnourished adolescent rats.

Young growing animals appear to have significantly reduced "nutritional to short periods of unstressed starvation compared with adults, with resultant growth arrest and/or atrophy of diaphragm (Dia) muscle fibers. The aim of this study was to assess in an adolescent rat model of acute nutritional deprivation (ND; 72 h) the impact of insulin-like growth factor I (IGF-I), with or without added growth hormone (GH), on the cross-sectional areas (CSA) of individual Dia muscle fibers. Five groups were studied: 1) control (Ctr); 2) ND; 3) ND given IGF-I (ND/IGF-I); 4) ND given GH (ND/GH); and 5) ND given a combination of IGF-I and GH (ND/IGF-I/GH). IGF-I was given by a subcutaneously implanted osmotic minipump (200 microg/day), whereas GH was administered twice daily by a subcutaneous injection (250 microg every 12 h). Isometric contractile and fatigue properties of the Dia were determined in vitro. Forces were normalized for muscle CSA (i.e., specific force). Dia fiber type proportions were determined histochemically, and fiber CSA was quantified by using a computer-based image-processing system. Total serum IGF-I concentrations were significantly reduced in ND and ND/GH animals, compared with Ctr, and elevated in the groups receiving IGF-I. The provision of growth factors did not alter the contractile or fatigue properties of ND animals. Dia fiber type proportions were similar among the groups. In ND animals, there was a significant reduction in the CSA of types I, IIa, IIx, and IIc Dia fibers compared with Ctr. The administration of IGF-I alone or in combination with GH to ND animals significantly diminished the reduction in Dia fiber size. GH alone had no effect on Dia fiber size in ND animals. We conclude that with acute ND the peripheral resistance to the action of GH appears to be bypassed by the administration of IGF-I alone or in combination with GH.

Animals↗

Anabolic influences of insulin-like growth factor I and/or growth hormone on the diaphragm of young rats.

It is controversial whether insulin-like growth factor I (IGF-I), growth hormone (GH), or their combination might enhance body growth and/or tissue anabolism in the well-fed animal with an intact somatotrophic axis. To assess this further, we studied four groups of adolescent rats: 1) control (Ctr), 2) GH, 3) IGF-I, and 4) GH/IGF-I. IGF-I was given via an osmotic minipump, whereas GH was injected subcutaneously for a period of 72 h. Diaphragm (Dia) contractile and fatigue properties were determined in vitro. Quantitative histochemical and morphometric analyses were performed on Dia fibers. Total serum IGF-I levels were significantly increased in the groups receiving growth factors. Although body weight increased to a greater extent in the animals receiving growth factors, a further synergistic effect was noted in the GH/IGF-I animals compared with either GH or IGF-I groups. Costal Dia mass was greater in the groups receiving growth factors. The Dia of GH/IGF-I animals was more fatigue resistant than the Dia in Ctr. The cross-sectional area of types IIa and IIx fibers were increased to a similar extent in all groups receiving growth factors compared with Ctr. Succinate dehydrogenase activity of type IIa fibers was significantly greater in the GH/IGF-I animals compared with the other groups. We conclude that the short-term provision of growth factors to well-nourished, normally growing adolescent rats can accelerate body growth and promote selective hypertrophy of predominantly type II Dia fibers.

Animals↗

Late-life depression: how to make a difficult diagnosis.

Approximately 15% of persons age 65 and older have major depression. Risk factors include a recent loss (eg, widowhood or mastectomy), living alone, co-morbidities (eg, hypertension, stroke, cognitive deficits), and drug interactions. Warning signs of depression may include weight loss, sleep problems, feelings of guilt or worthlessness, loss of interest in sexual relations, or changes in activities of daily living. The diagnosis of depression is easy to miss if the physician doesn't look for it, because older persons often don't mention feeling depressed. Yet undetected depression can be deadly for older patients, who have the highest rate of suicide among all Americans. Plans for suicide may be direct or covert, as in not eating or not taking heart medication.

Age Distribution↗

Late-life depression: treatment strategies for primary care practice.

Most patients age 65 and older with symptoms of depression respond well to treatment. Choices of therapy include medications, electroconvulsive therapy (ECT), and psychotherapy. Every primary care physician should be comfortable with using at least two or three medicines from different drug classes. The likelihood of side effects depends on the antidepressant prescribed and other medications the patient might be taking. The combination of medication with psychotherapy appears more effective than one or the other alone. ECT is the treatment of choice when rapid results are needed (eg, if the patient is suicidal or losing weight quickly and in danger of a medical crisis). The physician/patient relationship can be a strong antidepressant.

Aged↗

An economic profile of American older women.

This literature review examines the economic status of American women age 65 and older in view of their longevity, employment patterns, sources of income, income levels, potential for poverty, and their economic stake in current public policy debates and actions regarding Social Security, Medicare, Medicaid, and SSI. Although women live longer and therefore must stretch their financial resources further than men, longevity is not the sole cause of their economic vulnerability. Rather, it is associated with historical patterns of economic dependence on men; with sporadic, often low-wage or nonexistent employment histories; and with public policies and programs that place undue financial pressures on older women. Living alone is a major risk factor for poverty, and women of color are doubly at risk, with the highest poverty rates of all the elderly. Middle-class women face the possibility of "cycling into poverty" after widowhood, especially if their husbands suffered long, costly illnesses or spousal pensions shrink or disappear. While women's improving educational and work opportunities are likely to result in improved financial circumstances for future generations of older women, it will be necessary to move beyond their personal efforts to the public policy arena for solutions to the often devastating effects of uninsured health care costs, pension inequities, and other pressing economic concerns for older women.

Aged↗

Interactive effects of denervation and malnutrition on diaphragm structure and function.

The purpose of this study was to examine the interactive effects of unilateral denervation (DN) and prolonged malnutrition (MN) on the structure and function of the diaphragm muscle (Dia). Four groups of rats were studied: control (Con), MN, DN, and DN-MN. MN began 2 wk after DN and lasted 4 wk. In both the DN and DN-MN groups, the relative loss in Dia weight exceeded the relative change in body weight. Compared with the Con group, Dia specific force was reduced by approximately 40% in both the DN and DN-MN groups but was unaffected in the MN group. Dia fatigue resistance improved in all experimental groups but to a greater extent in the DN and DN-MN groups. In both the DN and DN-MN groups, approximately 50% of Dia fibers were classified as type IIc, whereas fiber type proportions did not change in the MN group. In the DN group, only type IIb/x fibers atrophied, whereas all fiber types atrophied in the MN and DN-MN groups. We conclude that in the DN-MN group the reduction in specific force combined with the reduction in total cross-sectional area of the muscle significantly curtails Dia force-generating capacity.

Animal Nutritional Physiological Phenomena↗

Functional role and structure of the scalene: an accessory inspiratory muscle in hamster.

Although the scalene muscle (Sca) is a primary inspiratory muscle in humans, its respiratory function in other species is less clear. The electromyographic (EMG) activity of the Sca was studied during resting ventilation (eupnea) in both the awake and anesthetized hamster and after a variety of respiratory challenges in the anesthetized animal. The EMG activities of the medial Sca and the costal diaphragm were compared. The medial Sca, the major component of the Sca, originates from cervical transverse processes 2 to 5 and inserts primarily onto rib 4, with a small segment onto rib 3. In both the anesthetized and awake animal, the Sca was always silent during quiet breathing. With CO2-stimulated hyperpnea, the Sca was always recruited during inspiration in phase with the diaphragm. Active recruitment of the Sca was also observed after resistive loading and total airway occlusion. After ipsilateral phrenicotomy, the Sca was persistently recruited during eupnea. The specificity of the EMG signals was tested both by excluding cross contamination from other rib cage muscles and by selective denervation studies. Muscle spindles were identified in the medial Sca histochemically, suggesting that the respiratory activity of the Sca can also be modulated by changes in muscle length and/or load. These results indicate that the Sca functions as an accessory inspiratory muscle in the hamster and may play an important role in conditions of chronic load.

Animals↗

Late-life depression: when and how to intervene.

Late-life depression ranges from mild to severe and can lead to significant physical and social limitations. Up to one-third of patients with medical disorders also suffer from depressive symptoms. Differential diagnosis of depression is often confounded by medical conditions that impair cognitive functioning, such as Alzheimer's disease and vascular dementia. Depression is a modifiable risk factor for suicide in old age. Once diagnosed, depression is a highly treatable disease. Treatment modalities include psychotherapy, antidepressants, and electroconvulsive therapy for intractable cases. Many patients are now being treated in primary care settings, due to managed care limits on referrals and to patient reluctance to seek psychiatric care.

Age Factors↗

Interactive effects of emphysema and malnutrition on diaphragm structure and function.

Interactive effects of emphysema (EMP) and prolonged nutritional deprivation (ND) on contractile, morphometric, and metabolic properties of hamster diaphragm muscle (DIA) were examined. Six months after induction of EMP (intratracheal elastase), saline-treated controls (CTL) and EMP hamsters of similar body weights were subjected to ND over 6 wk. Isometric contractile and fatigue properties of costal DIA were determined in vitro. DIA fibers were histochemically classified as type I or II, and fiber succinate dehydrogenase activity and cross-sectional area were determined using quantitative microscopic procedures. From histochemical sections, the number of capillaries per fiber (C/F) and per fiber cross-sectional area (C/A) were determined. ND resulted in progressive loss of body weight (ND-CTL, 23.8%; ND-EMP, 28.4%; P = NS). ND did not affect reduction in optimal length (Lo) of DIA fibers in EMP compared with CTL and ND-CTL hamsters. Maximum specific force (i.e., force/unit area) was reduced by approximately 25% in EMP animals compared with CTL. ND did not improve or exacerbate the reduction in specific force with EMP. ND attenuated improved fatigue resistance of DIA in EMP animals. No differences in fiber type proportions were noted among experimental groups. Significant atrophy of type I and II DIA fibers was noted after ND. Atrophy was proportionately greater in type II fibers of ND-EMP when referenced to EMP animals. Thus adaptive hypertrophy of type II DIA fibers in EMP animals was abolished. Fiber succinate dehydrogenase activity was significantly increased in type I and II fibers in EMP DIA. ND did not affect this metabolic adaptation of DIA fibers to persistent loads imposed by EMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pressure↗

The relationship between oxygen consumption and work rate in patients with airflow obstruction.

The oxygen cost of augmented ventilation is increased in patients with chronic obstructive pulmonary disease, either at rest or during exercise. Thus, if excessive demands are placed on the respiratory muscles during exercise in these patients, we postulate that the total oxygen consumption (VO2) may increase relative to the work rate compared to control subjects. The aim of this study was to examine the relationship between VO2 and work rate during exercise in patients with airflow obstruction. A retrospective analysis of data collected over 7 years was conducted. Patients with airflow obstruction (n = 131) were compared and contrasted with those in whom pulmonary function studies (spirometry, lung volumes) were normal (n = 199). Severity of airflow obstruction (ie, mild moderate, severe) was determined, using the 95 percent confidence limits for the ratio of FEV1 to FVC. Incremental exercise studies were performed on a cycle ergometer. Resting VO2 was not significantly different across the groups with airflow obstruction measured either directly or normalized for body weight. The VO2max was significantly reduced in the patients with severe airflow obstruction, compared with the normal group, as well as the patients with mild and moderate airflow obstruction. No differences were noted in the slope of VO2 plotted against work rate in the patients with airflow obstruction (regardless of the severity of the obstruction) and individuals in whom results of pulmonary function tests were normal. In addition, when gender was taken into account, there was essentially no difference in the slopes for either male or female subjects across all groups. Stepwise, linear regression failed to demonstrate any variable or variables that were strongly related to slope. We postulate that the maintenance of a normal slope of VO2 on work rate in patients with airflow obstruction, in whom the oxygen cost and work of breathing is likely increased, may mask a significant reduction in nonrespiratory VO2 (for example, to exercising skeletal muscles).

Aged↗